Microtubule buckling in an elastic matrix with quenched disorder

The intracellular elastic matrix has been recognized as an important factor to stabilize microtubules and increase their critical buckling force in vivo. This phenomenon was qualitatively explained by the Winkler model, which investigated buckling of a filament embedded in a homogeneous elastic medium. However, the assumption of homogeneity of the matrix in Winkler's, and other advanced models, is unrealistic inside cells, where the local environment is highly variable along the filament. Considering this to be a quenched-disorder system, we use a Poisson distribution for confinements, and apply the replica technique combined with the Gaussian variational method to address the buckling of a long filament. The results show two types of filament buckling: one corresponding to the first-order, and the other to a continuous second-order phase transition. The critical point, i.e. the switch from first- to second-order buckling transition, is induced by the increase in disorder strength. We also discover that this random disorder of the elastic environment destabilizes the filament by decreasing $P_c$ from the Winkler result, and the matrix with stronger mean elasticity has a stronger role of disorder (inhomogeneity). For microtubules in vivo, buckling follows the discontinuous first-order transition, with the threshold reduced to the fraction between 0.9 and 0.75 of the Winkler prediction for the homogeneous elastic matrix. We also show that disorder can affect the force-displacement relationship at non-zero temperature, while at zero temperature this effect vanishes.This work has been supported by the Theory of Condensed Matter Critical Mass Grant from EPSRC (EP/J017639)

Stiffening of under-constrained spring networks under isotropic strain

Disordered spring networks are a useful paradigm to examine macroscopic mechanical properties of amorphous materials. Here, we study the elastic behavior of under-constrained spring networks, i.e.\ networks with more degrees of freedom than springs. While such networks are usually floppy, they can be rigidified by applying external strain. Recently, an analytical formalism has been developed to predict the mechanical network properties close to this rigidity transition. Here we numerically show that these predictions apply to many different classes of spring networks, including phantom triangular, Delaunay, Voronoi, and honeycomb networks. The analytical predictions further imply that the shear modulus $G$ scales linearly with isotropic stress $T$ close to the rigidity transition; however, this seems to be at odds with recent numerical studies suggesting an exponent between $G$ and $T$ that is smaller than one for some network classes. Using increased numerical precision and shear stabilization, we demonstrate here that close to the transition linear scaling, $G\sim T$, holds independent of the network class. Finally, we show that our results are not or only weakly affected by finite-size effects, depending on the network class.Comment: 17 pages, 10 figure

Hard-wall entropic effect accelerates detachment of adsorbed polymer chains.

Many previous studies of unbinding kinetics have focused on a two-state model, with fully bonded and free states, which may not extend to more complicated biopolymer dynamics involving other reactions. Here we address the kinetic rate of this process at the segment level, as it is influenced by a growing dangling end of the chain. We use the mean first-passage time approach and treat the polymer as a chain attached to a wall through a succession of spring potentials, with two distinct regions of bonded and free segments. The interaction between the wall and free-moving chain end adds an entropic repulsion to this process. We estimate the average monomer detachment rate K as a function of the free dangling length L. For a flexible polymer, we find an acceleration factor in the average detachment rate depending on L and the details of the spring bond; when L is long, this factor is a simple ratio of its breaking distance to the natural bond length. For a semiflexible filament, we examine the regime where L is shorter than persistence length L_{p}, as the limit opposite to that of the flexible chain. An enhancing factor also appears, speeding up the filament unbinding when the free length grows; for a long rigid rod, this factor becomes two, independently of the bond details. We also examine the total unbinding time of an irreversible detaching process by integrating (1/K) over polymer length and discover that its power-law scaling with chain length is smaller than one, over the commonly seen range of polymer size.This work is funded by the Theory of Condensed Matter Critical Mass Grant from EPSRC (EP/J017639)

Examining the Factors Influencing Consumers’ Purchasing Intention for Genetically Modified Agricultural Food

The application of genetic engineering to food is becoming popular worldwide, especially in UK and USA. However, consumers in Asia remain unsure of the risks and benefits of genetically modified food. To measure the purchase intentions of Taiwanese and Vietnamese consumers using an integrated framework of the attitude model and the behavioral intention model, quantitative research was conducted in which the questionnaires were distributed to respondents living in Taiwan and in Vietnam. The results showed that the dependent variable of consumer attitude was positively impacted by three in-dependent variables including perceived risk to health, perceived benefit to health, and perceived benefit to the environment. The other construct showed no significant effect on consumers’ attitudes in the two countries. The consistency result in both countries between subjective norm and attitude revealed a positive impact on the purchase intention in descending order, while the variable of perceived behavioral control did not contribute to affecting purchase intention significantly. Finally, limitations and suggestions for future studies are also proposed

Structural effects of cap, crack, and intrinsic curvature on the microtubule catastrophe kinetics.

Microtubules (MTs) experience an effect called "catastrophe," which is the transition from the MT growth to a sudden dramatic shrinkage in length. The straight guanosine triphosphate (GTP)-tubulin cap at the filament tip and the intrinsic curvature of guanosine diphosphate (GDP)-tubulins are known to be the key thermodynamic factors that determine MT catastrophe, while the hydrolysis of this GTP-cap acts as the kinetic control of the process. Although several theoretical models have been developed, assuming the catastrophe occurs when the GTP-cap shrinks to a minimal stabilizing size, the structural effect of the GTP-cap and GDP-curvature is not explicitly included; thus, their influence on catastrophe kinetics remains less understood. To investigate this structural effect, we apply a single-protofilament model with one GTP-cap while assuming a random hydrolysis mechanism and take the occurrence of a crack in the lateral bonds between neighboring protofilaments as the onset of the catastrophe. Therein, we find the effective potential of the tip along the peel-off direction and formulate the catastrophe kinetics as a mean first-passage time problem, subject to thermal fluctuations. We consider cases with and without a compressive force on the MT tip, both of which give a quadratic effective potential, making MT catastrophe an Ornstein-Uhlenbeck process in our formalism. In the free-standing case, the mean catastrophe time has a sensitive tubulin-concentration dependence, similar to a double-exponential function, and agrees well with the experiment. For a compressed MT, we find a modified exponential function of force that shortens the catastrophe time.EPSRC EP/J01763

Bis(μ-trimethyl­silanolato-κ2 O:O)bis­{[2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentyl­phenolato-κ2 N,O]zinc}

The binuclear title complex, [Zn2(C22H28N3O)2(C3H9OSi)2], has a crystallographic imposed centre of symmetry. The ZnII atom is coordinated by three O and one N atom from one 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentyl­phenolate ligand and two bridging trimethyl­silanolate anions in a distorted tetra­hedral geometry. The dihedral angle between the benzotriazole ring system and the benzene ring is 19.83 (5)°. The tert-pentyl groups are disordered over two orientations with refined site-occupancy ratios of 0.858 (4):0.142 (4) and 0.665 (6):0.335 (6)

Cellular apoptosis susceptibility (CSE1L/CAS) protein in cancer metastasis and chemotherapeutic drug-induced apoptosis

The cellular apoptosis susceptibility (CSE1L/CAS) protein is highly expressed in cancer, and its expression is positively correlated with high cancer stage, high cancer grade, and worse outcomes of patients. CSE1L (or CAS) regulates chemotherapeutic drug-induced cancer cell apoptosis and may play important roles in mediating the cytotoxicities of chemotherapeutic drugs against cancer cells in cancer chemotherapy. CSE1L was originally regarded as a proliferation-associated protein and was thought to regulate the proliferation of cancer cells in cancer progression. However, the results of experimental studies showed that enhanced CSE1L expression is unable to increase proliferation of cancer cells and CSE1L regulates invasion and metastasis but not proliferation of cancer cells. Recent studies revealed that CSE1L is a secretory protein, and there is a higher prevalence of secretory CSE1L in the sera of patients with metastatic cancer. Therefore, CSE1L may be a useful serological marker for screening, diagnosis and prognosis, assessment of therapeutic responses, and monitoring for recurrence of cancer. In this paper, we review the expression of CSE1L in cancer and discuss why CSE1L regulates the invasion and metastasis rather than the proliferation of cancer

Bevacizumab Dose Affects the Severity of Adverse Events in Gynecologic Malignancies

In this retrospective study, we investigated adverse events and outcomes in patients treated with bevacizumab for ovarian, fallopian tube, or primary peritoneal cancers at a single hospital. We determined the cumulative incidences of various bevacizumab-related adverse events and the correlation between dose and adverse event incidences. We analyzed data from 154 patients that received 251 rounds of bevacizumab as first-line, first salvage, >2 salvage treatments. Adverse events of any grade were observed in 121 (78.6%) patients; at least one grade 3 or 4 adverse event occurred in 32 (20.8%) patients. The two most common events were proteinuria (38.3%) and hypertension (33.8%). The first-line treatment group displayed significantly higher frequencies of hypertension (52.7% vs. 18.9% vs. 15.5%, p < 0.001), wound complications (9.1% vs. 0% vs. 1.2%, p = 0.010), arthralgia (29.1% vs. 11.3% vs. 8.3%, p = 0.003), and reduced range of joint motion (14.5% vs. 5.7% vs. 3.6%, p = 0.046), compared to those in the first and >2 lines salvage groups, respectively (Kruskal–Wallis test). The cumulative incidences of all grades and grades 3/4 of hypertension cumulative incidence plateaued at around 30% for all grades and 10% for grades 3 and 4, at bevacizumab doses above 8080 and 3510 mg, respectively. The proteinuria cumulative incidence plateaued at around 35% for all grades and 3% for grades 3 and 4, at bevacizumab doses above 11,190 and 4530 mg, respectively. We concluded that, in this realistic clinical population, different kinds and higher cumulative incidences of adverse events were observed compared to those reported in previous clinical trials. Moreover, bevacizumab doses showed cumulative toxicity and plateau effects on hypertension and proteinuria